Age-related alterations in noradrenergic input to the hippocampal formation: structural and functional studies in...

Intrinsic versus extrinsic determinants of age-related alterations in hippocampal noradrenergic transmission were investigated using intraocular allografts in rats. Three groups of animals were examined: young hippocampal transplants in young hosts, old transplants in old hosts and young transplants in old hosts. Postsynaptic sensitivity to noradrenaline (NA) was measured by extracellular recordings of spontaneous activity and superfusion with known concentrations of catecholamines in the anterior chamber of the eye. Hill plots demonstrated that the dose-response relationships of NA-induced depressions were linear and parallel in the 3 groups. Aged hippocampal grafts displayed a highly significant subsensitivity to NA of one order of magnitude. The EC50 for this group was 203.1 microM as compared to 29.2 in young grafts. Young intraocular grafts in old hosts responded similarly to transplants in young hosts, with an EC50 of 32.4 microM for the depressant actions of NA. Collaterals of the host iris sympathetic ground plexus invaded the hippocampal grafts. The density of this noradrenergic innervation was estimated by immunohistochemistry for tyrosine hydroxylase. A slightly increased density and fluorescence intensity of the noradrenergic fibers were observed in the old transplants as compared to the young transplants in young and old hosts. This was correlated with a significantly (P less than 0.01) increased content of NA in old transplants, as measured with high performance liquid chromatography. The old transplants also contained a large number of autofluorescent lipofuchsin granules, which were absent in the young transplants, regardless of the recipient age. Taken together, these results suggest the existence of alterations in pre- as well as postsynaptic noradrenergic mechanisms in the aging hippocampus. These changes were dependent on transplant age rather than host age, thus suggesting an involvement of intrinsic rather than extrinsic determinants in this model system.